Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study

Qin, Shukui; Chan, Stephen L.; Cheng, Ann‐Lii; Kaseb, Ahmed O.; Vogel, Arndt; Gu, Shanzhi; Bai, Yuxian; Ren, Zhigang; Lin, Xinhua; Chen, Zhendong; Jia, Weidong; Jin, Yongdong; Guo, Yanju; Hu, Xiaohua; Meng, Zhiqiang; Liang, Jun; Cheng, Ying; Xiong, Jianping; Ren, Hong; Yang, Fang; Li, Wei; Chen, Yajin; Zeng, Yong; Султанбаев, А. В.; Pazgan−Simon, Monika; Pisetska, Margaryta; Melisi, Davide; Ponomarenko, Dmitriy M.; Osypchuk, Yurii; Sinielnikov, Ivan; Yang, Tsung‐Ming; Xiao, Liang; Chen, Chunxia; Wang, Linna; Zhang, Mingxiang; Xu, Li; Yuan, Xianglin; Li, Da; Ying, Jianming; Zhang, Jingdong; Zhang, Tao; Gu, Kai; He, Yong; Ping, Hao; Jiang, Da; Zhang, Shu; Xing, Baocai; Zhang, Baihong; Wang, Dong; Zhai, Xiaofeng; Liang, Houjie; Cybulska-Stopa, Bożena; Dvorkin, Mikhail; Stroyakovskiy, Daniil; Nechaeva, M.; Yen, Chia‐Jui; Su, Wei‐Wen; Chen, Yen‐Hao; Bondarenko, Igor; Yang, Lin; Fang, Weijia; Gómez‐Martín, Carlos; Ryu, Min‐Hee; Kim, Han-Sang; Kim, Jeehyun; Zarubenkov, Oleg; Орлова, Р. В.; Poddubskaya, Elena; Fadeeva, Natalia; Makarova, Yulia; Chao, Yee; Hung, Chao‐Hung; Neffa, Maryna; Vynnychenko, О. І.; Burgoyne, Adam M.; Hao, Chunyi; Mohr, Raphael; Díaz‐Beveridge, Roberto; Feliú-Batlle, Jaime; Cubillo-Gracian, Antonio; Lee, Ann‐Shing; Daniele, Bruno; Antonuzzo, Lorenzo; Sangiovanni, A.; Gasbarrini, Antonio; Scartozzi, Mario; Ahn, Mi Sun; Oh, Sung‐Yong; Орлов, С. В.; Harputluoğlu, Hakan; Öksüzoğlu, Berna; Hsu, Chiun; Rau, Kun‐Ming; Krechkovskyi, Oleksandr; Yareshko, V.G.; Xiong, Henry Q.; Lee, Fa-Chyi; Jiang, Yixing; Gabayan, Afshin Eli; Crow, Mary K.; Steenkiste, Christophe Van; Verset, Gontran

doi:10.1016/s0140-6736(23)00961-3

Cited by 234 publications

(83 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a recent phase III randomized control trial of camrelizumab (PD-1 inhibitor) and rivoceranib (selective VEGFR-2 inhibitor) versus sorafenib, there was a significant improvement in median overall survival (22.1 mo vs. 15.2 mo), and there was a 38% reduction in the risk of death (HR, 0.62). Median progression-free survival with camrelizumab and rivoceranib was 5.6 months compared with 3.7 months for sorafenib, which was a 48% reduction in the risk of progression or death (HR, 0.52; 95% CI, 0.41–0.65; p < 0.0001) 54 . This study establishes camrelizumab and rivoceranib as potentially viable treatment options moving forward.…”

Section: Treatmentmentioning

confidence: 70%

“…Median progression-free survival with camrelizumab and rivoceranib was 5.6 months compared with 3.7 months for sorafenib, which was a 48% reduction in the risk of progression or death (HR, 0.52; 95% CI, 0.41-0.65; p < 0.0001). [54] This study establishes camrelizumab and rivoceranib as potentially viable treatment options moving forward.…”

Section: Camrelizumab and Rivoceranibmentioning

confidence: 77%

“…CURRENT Imbrave 150 [52] Positive HIMALAYA [42] Positive RESCUE [43] First-line Camrelizumab + Apatinib SHR-1210-III-310 [54] Positive for overall survival Camrelizumab + Rivoceranib COSMIC-312 [55] Positive recommended as first-line therapy, can be considered in patients with contraindications to sorafenib monotherapy. [60] Other single-agent options, including tislelizumab (anti-PD-1 monoclonal antibody)-based on the phase 3 RATIONALE 301 trial-and durvalumab monotherapy, have also had favorable results.…”

Section: Drugmentioning

confidence: 99%

See 2 more Smart Citations

Current updates in HCC screening and treatment

Hunold,

Pillai

2023

Clinical Liver Disease

View full text Add to dashboard Cite

Section: Treatmentmentioning

confidence: 70%

Section: Camrelizumab and Rivoceranibmentioning

confidence: 77%

Section: Drugmentioning

confidence: 99%

See 1 more Smart Citation

Current updates in HCC screening and treatment

Hunold,

Pillai

2023

Clinical Liver Disease

View full text Add to dashboard Cite

“…19 Combining immunotherapy with targeted therapy has also emerged as a promising approach. 20 As reported by the IMbrave150 clinical trial, 21 atezolizumab plus bevacizumab resulted in superior survival benefits compared to sorafenib for unresectable HCC patients (median OS: 19.2 vs 3.4 months, descriptive P < 0.001; median PFS: 6.9 vs 6 these findings provided more novel and effective treatment modalities for HCC patients. However, local recurrences after curative treatment and distant metastasis to bone, lung, and lymph nodes are the main reasons for treatment failure.…”

Section: Discussionmentioning

confidence: 82%

“…5 More recently, camrelizumab (an anti-programmed cell death protein-1 [PD-1] antibody) plus rivoceranib (an anti-angiogenic tyrosine-kinase inhibitor) showed encouraging survival benefits for unresectable HCC. 6 Currently, EBRT, especially for stereotactic body radiotherapy (SBRT), has emerged as an alternative approach to intermediate and advanced HCC, with the advantage of higher precision of radiation delivery, and less toxicity to the surrounding normal tissues, 7 even for those who diagnosed with Barcelona clinical liver cancer (BCLC) stage-C, palliative SBRT is an effective and safe treatment modality. 8 Previous studies have demonstrated the high efficacy and well-tolerance of SBRT alone for the treatment of primary liver cancer, as well as extrahepatic metastases.…”

Section: Introductionmentioning

confidence: 99%

Lymphocyte-to-C Reactive Protein Ratio is an Independent Predictor of Survival Benefits for Hepatocellular Carcinoma Patients Receiving Radiotherapy

Shi,

Zhu,

Jin

et al. 2024

JHC

View full text Add to dashboard Cite

Background: Stereotactic body radiotherapy (SBRT) has emerged as an alternative approach for patients with hepatocellular carcinoma (HCC), and we aim to find potential prognostic biomarkers for HCC patients who received SBRT. Methods: In this study, we retrospectively analyzed HCC patients who underwent SBRT in our institution from January 2018 to December 2022. The inflammatory parameters, along with baseline patients' characteristics were collected to elucidate the potential relationship with survival benefits and liver toxicities. Results: Overall, 35 patients were enrolled in our study. For the efficacy population (25 patients who underwent SBRT for primary liver lesions), the objective response rate (ORR) and disease control rate (DCR) were 60% and 100%, respectively. The median progression-free survival (PFS) was 9.9 months [95% confidence interval (CI) 5.6-14.1 months], and the median overall survival (OS) was 18.5 months (95% CI 14.2-22.8 months). We further confirmed that higher baseline lymphocyte-C-reactive protein ratio (LCR) (≥2361.11) was positively related to both longer PFS (12.0 vs 4.3 months, P = 0.002) and OS (21.9 vs 11.4 months, P = 0.022). Moreover, patients with diabetes and higher alpha-fetoprotein (AFP) (≥400 ng/mL) were also found to be associated with worse OS. The most common hepatotoxicity was elevated gamma-glutamyl transferase (GGT) (84.0%). Conclusion:In conclusion, for patients with inoperable HCC, SBRT resulted in satisfactory local control, survival benefits, and acceptable liver toxicity. Pre-radiotherapy LCR might be an independent and readily available predictor for survival, which facilitates us to find the most appropriate treatment options.

show abstract

Camrelizumab vs Placebo in Combination With Chemotherapy as Neoadjuvant Treatment in Patients With Early or Locally Advanced Triple-Negative Breast Cancer

Chen,

Li,

Zhang

et al. 2024

JAMA

View full text Add to dashboard Cite

ImportancePreferred neoadjuvant strategies for early or locally advanced triple-negative breast cancer include a 4-drug chemotherapy regimen containing anthracyclines, cyclophosphamide, taxanes, and platinum. Blockade of the programmed death receptor 1/ligand-1 (PD-1/PD-L1) pathway may improve efficacy of classic neoadjuvant chemotherapy. Camrelizumab, an anti–PD-1 antibody, has showed antitumor activity in advanced triple-negative breast cancer.ObjectiveTo evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as neoadjuvant therapy for patients with early or locally advanced triple-negative breast cancer.Design, Setting, and ParticipantsThis randomized, double-blind, phase 3 trial enrolled patients from 40 hospitals in China between November 25, 2020, and May 12, 2023 (data cutoff: September 30, 2023). A total of 441 eligible patients were enrolled.InterventionsPatients were randomized in a 1:1 ratio to receive either camrelizumab 200 mg (n = 222) or placebo (n = 219) combined with chemotherapy every 2 weeks. The chemotherapy included nab-paclitaxel (100 mg/m2) and carboplatin (area under the curve, 1.5) on days 1, 8, and 15 in 28-day cycles for the first 16 weeks followed by epirubicin (90 mg/m2) and cyclophosphamide (500 mg/m2) every 2 weeks for 8 weeks.Main Outcomes and MeasuresThe primary end point was pathological complete response (defined as no invasive tumor in breast and lymph nodes [ypT0/Tis ypN0]).ResultsAmong 441 females randomized (median age, 48 years), the median (range) follow-up duration from randomization was 14.4 (0.0-31.8) months. Pathological complete response was achieved in 126 patients (56.8% [95% CI, 50.0%-63.4%]) in the camrelizumab-chemotherapy group and 98 patients (44.7% [95% CI, 38.0%-51.6%]) in the placebo-chemotherapy group (rate difference, 12.2% [95% CI, 3.3%-21.2%]; 1-sided P = .004). In the neoadjuvant phase, adverse events of grade 3 or higher occurred in 198 patients (89.2%) in the camrelizumab-chemotherapy group and 182 (83.1%) in the placebo-chemotherapy group; serious adverse events occurred in 77 patients (34.7%) in the camrelizumab-chemotherapy group and 50 (22.8%) in the placebo-chemotherapy group, with fatal adverse events occurring in 2 patients (0.9%) in the camrelizumab-chemotherapy group.Conclusions and RelevanceAmong patients with early or locally advanced triple-negative breast cancer, the addition of camrelizumab to neoadjuvant chemotherapy significantly improved pathological complete response.Trial RegistrationClinicalTrials.gov Identifier: NCT04613674

show abstract

Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study

Cited by 234 publications

References 43 publications

Current updates in HCC screening and treatment

Current updates in HCC screening and treatment

Lymphocyte-to-C Reactive Protein Ratio is an Independent Predictor of Survival Benefits for Hepatocellular Carcinoma Patients Receiving Radiotherapy

Camrelizumab vs Placebo in Combination With Chemotherapy as Neoadjuvant Treatment in Patients With Early or Locally Advanced Triple-Negative Breast Cancer

Contact Info

Product

Resources

About